Surgical Treatment for Octogenarians with Lung Cancer: Results from a Population-Based Series of 124 Patients

ORIGINAL ARTICLE

Surgical Treatment for Octogenarians with Lung Cancer: Results from a Population-Based Series of 124 Patients Hes A. P. Brokx, MD,* Otto Visser, MD, PhD,‡ Pieter E. Postmus, MD, PhD,* and Marinus A. Paul, MD, PhD†

Introduction: With the increasing life span in the Western world, the number of octogenarians with resectable, localized non-small cell lung cancer is increasing. Previous reports on the outcome of surgery for lung cancer in octogenarians were mainly derived from single institutions. In contrast, this study presents results for all hospitals in a region of 3 million inhabitants. Methods: General data on all patients diagnosed with lung cancer in the period 1989 to 2004 were retrieved from the Amsterdam Cancer Registry. Incidence and type of treatment were tabulated and tested for significance with ␹2 analysis. Survival was calculated using actuarial analysis. Absolute and relative survival for octogenarians relative to other age groups and relative to other treatment modalities in octogenarians with clinical stage I/II lung cancer was performed. Results: Non-small cell lung cancer was diagnosed in 1993 octogenarians (14% of all lung cancer patients). One hundred twentyfour patients (6%) underwent surgery. Five patients died within 30 days of surgery (4%). Relative survival after 1, 2, and 5 years was 83%, 69%, and 47%, respectively. These relative survival figures are comparable with other age groups. There was a survival benefit for surgical resection versus radiotherapy and other or no treatment (relative 5-year survival of 47% versus 3% and 0%, respectively). Conclusions: Resection rates in octogenarians are low but satisfactory postoperative mortality and acceptable survival suggest that selection criteria should be adapted. Until effective alternative treatment becomes available, surgical resection, preceded by a thorough preoperative assessment, should be considered in the “old but fit” octogenarian. Key Words: Surgery, Octogenarians, Lung cancer. (J Thorac Oncol. 2007;2: 1013–1017)

N

on-small cell lung cancer (NSCLC) represents 80% of all lung cancers and, like most other cancers, is a disease of advanced age.1 Because of the longer life span in the

Departments of *Pulmonology and †Surgery, VU University Medical Center, Amsterdam, The Netherlands; and ‡Comprehensive Cancer Center, Amsterdam, The Netherlands. Disclosure: The authors report no conflict of interest. Address for correspondence: Marinus A. Paul, MD, PhD, Department of Surgery, VU University Medical Center, P.O. Box 7057, 1007 MB Amsterdam, The Netherlands. E-mail: [email protected] Copyright © 2007 by the International Association for the Study of Lung Cancer ISSN: 1556-0864/07/0211-1013

Western world, the number of elderly patients with NSCLC is increasing. For limited tumors, surgery is the treatment of choice. Due to advances in anesthesia and postoperative care, surgery can now be performed in high-risk patients and even in those of 80 years and older (octogenarians).2,3 Age-related differences in both diagnostic procedures and treatment have already been reported,4,5 as well as the limited participation of elderly patients in clinical trials.6,7 A number of studies report on the use of surgery for elderly patients with lung cancer, but these are mainly derived from single, dedicated institutions. Little is known about the treatment and outcome of NSCLC in advanced age groups outside these specialized centers. In this report, we present resection rates and survival outcome for octogenarians with lung cancer who underwent resection in both general and university hospitals within a large region.

MATERIALS AND METHODS Data were retrieved from the Cancer Registry in Amsterdam. The current study was performed according to the Privacy Regulations of the Amsterdam Cancer Registry and approved by the Amsterdam Cancer Registry Board. The cancer registry collects information on all cancer diagnoses and treatment modalities directly from the medical records in an area with 3 million people (17% of the population in The Netherlands). The area comprises two university medical centers, 12 teaching hospitals, and nine district hospitals. Surgery for lung cancer is performed in 20 of the 23 hospitals. One university medical center and one teaching hospital have a department of cardiothoracic surgery. In the other hospitals, including the second university medical center, general surgeons perform lung cancer surgery. The median hospital volume is fewer than 20 operations per year.8 Tumors were classified according to the 1997 TNM classification. Considerations for surgical resection were in accordance with TNM stage and the patients’ comorbidities, performance status, and consent. However, exact details on comorbidities and presurgical selection were not separately collected. For the period 1989 to 2004, we studied the incidence of NSCLC per age group, the percentage of patients who underwent surgery, the type of resection, other treatments, and the survival outcome. We were able to determine observed and relative survival per age group and per

Journal of Thoracic Oncology • Volume 2, Number 11, November 2007

1013

Journal of Thoracic Oncology • Volume 2, Number 11, November 2007

Brokx et al.

treatment modality for the octogenarians group, within the Amsterdam Cancer Registry region. Relative survival is an estimation of disease-specific survival. It reflects survival of cancer patients, adjusted for survival in the general population with the same age structure. Relative survival is calculated as the ratio of the observed to the expected rates. Expected survival rates were calculated from life tables for the general population with the same age distribution. Chisquare analysis was used for proof of significance, and survival was calculated by actuarial analysis. The life expectancy for an 82-year-old person was estimated using national life tables.

RESULTS In the 16-year study period, NSCLC was diagnosed in 14,272 patients, of whom 1993 (14%) were 80 years and older (Table 1). Resection rates decreased with age from 30% for patients younger than 70 years to 23% for those aged 70 to 79 and 6% for octogenarians (p ⬍ 0.01). The group of octogenarians comprised 107 men and 17 women, with a mean age of 82 years (median, 82; range, 80 – 87 years) (Table 2). The most frequent operation was a lobectomy (n ⫽ 87). Four patients underwent a bilobectomy and 15 patients (12%) a pneumonectomy. A lesser resection was performed in six patients, and in the remaining 12 patients, the resection was not specified. The extent of lymph-node sampling or clearance during surgery was not recorded. Two patients received neoadjuvant chemotherapy. Lung surgery was performed in 20 of the 23 hospitals of the studied region. In two of these 20 hospitals, cardiothoracic surgeons performed lung surgery; in the other 18 hospitals, general surgeons performed lung resections. Each of these 20 hospitals treated elderly patients, with the number of resections varying from 1 to 16. Neither number nor the mortality rate per hospital could be obtained for publication, but mortality rates for lung surgery did not differ significantly between these hospitals (unpublished data). The majority of patients had clinical stage I or II disease. Six patients had clinical stage III disease, while three patients were classified as stage IV. Eight patients were up-staged at pathologic examination. (Table 3). Of the clinical stage IV patients, one had two sublobar lesions in two different lobes, which were resected in one session by two segmentectomies. The second patient was diagnosed with a diaphragmatic metastasis, which was resected with the pri-

TABLE 1. Frequency of NSCLC and Resection Rates by Age Group, 1989 to 2004 Age (y) ⬍50 50–59 60–69 70–79 80⫹ Total

1014

No. of Patients

%

No.

%

1036 2162 4061 5020 1993 14,272

7 15 28 35 14 100

354 885 1738 1507 124 4608

25 29 30 23 6 24

TABLE 2. Age Distribution of Octogenarians Who Underwent Resection, 1989 to 2004 (n ⫽ 124) Age (y)

80

81

82

83

84

85

86

87

No. of patients

37

25

28

21

6

3

2

2

TABLE 3. Patient, Tumor, and Treatment Characteristics of Surgically Treated Octogenarians, 1989 to 2004

Gender Male Female Histology Squamous cell carcinoma Adenocarcinoma Adenosquamous carcinoma Large cell carcinoma Sarcomatoid carcinoma Resection type Left pneumonectomy Right pneumonectomy Bilobectomy Lobectomy Sublobar resection Not specified c Stage (cTNM 1997) I–II III IV p Stage (pTNM 1997) IA IB IIA IIB IIIA IIIB IV Postoperative mortality No Yes

n

%

107 17

86 14

63 36 6 18 1

51 29 5 15 1

12 3 4 87 6 12

10 2 3 70 5 10

115 6 3

93 5 2

30 49 3 25 10 4 3

24 40 2 20 8 3 2

119 5

96 4

mary lesion. The last patient was diagnosed with a paraesophageal metastasis, which was also resected with the primary lesion. Five patients died postoperatively (4%). Of these, one underwent a right pneumonectomy. The observed and relative postoperative survival was 74% and 83% after 1 year, 55% and 69% after 2 years, and 24% and 47% after 5 years, respectively, for octogenarians (Table 4A). The general life expectancy for an 82 year old in The Netherlands is 5.9 years for men and 7.4 years for women. Relative 5-year survival rates for the total group of octogenarians with lung cancer relative to treatment modality were 47% in the surgical group, 3% in the radiotherapy group, and 0% in the other/nontreated group, respectively (Table 4B and Figure 1). Table 4C shows the same survival

Copyright © 2007 by the International Association for the Study of Lung Cancer

Journal of Thoracic Oncology • Volume 2, Number 11, November 2007 Surgical Treatment for Octogenarians with Lung Cancer

TABLE 4. Observed and Relative Survival Analyses of Amsterdam Cancer Registry Data, 1989 to 2004: A, Per Age Group after Surgical resection; B, for Octogenarians According to Treatment Modality; C, for Clinical Stage I/II Octogenarians According to Treatment Modality A. Observed and Relative Survival Rates After Surgical Resection Per Age Group Observed Survival

Relative Survival

Age Group

No.

1 yr

2 yr

5 yr

1 yr

2 yr

5 yr

⬍50 50–59 60–69 70–79 80⫹ Total

354 885 1738 1507 124 4608

83 86 81 75 74 80

68 72 64 59 55 64

53 52 44 37 24 43

84 87 82 79 83 82

68 73 67 66 69 68

54 54 49 50 47 51

B. Observed and Relative Survival Rates for Octogenarians According to Treatment Modality Observed Survival

Relative Survival

Treatment

No.

1 yr

2 yr

5 yr

1 yr

2 yr

5 yr

Resection Radiotherapy Other/none Total

124 592 1353 2069

74 34 15 24

55 14 5 10

24 2 0 2

83 39 17 27

69 18 6 13

47 3 0 4

C. Observed and Relative Survival Rates for Clinical Stage I/II Octogenarians According to Treatment Modality Observed Survival

Relative Survival

Treatment

No.

1 yr

2 yr

5 yr

1 yr

2 yr

5 yr

Resection Radiotherapy Other/none Total

115 225 332 672

73 47 23 40

54 20 8 20

26 3 1 6

82 54 26 45

69 26 11 26

52 6 2 11

it was 6% for the radiotherapy group and 2% for the other/no treatment group. The most interesting findings for this subset are the comparable relative survival for surgically treated octogenarians (i.e., 47%) to the younger age groups and the clear survival benefit of surgical resection in clinical stage I/II octogenarians as opposed to radiotherapy, no, or other treatment (i.e., 47% versus 6% and 2%, respectively).

DISCUSSION

FIGURE 1. Relative survival of octogenarians with lung cancer according to treatmentmodality, Amsterdam Cancer Registry, 1989 to 2004.

rates relative to treatment modality in octogenarians, although corrected for clinical stage I/II lung cancer. The relative 5-year survival rate for the resection group was 52%;

The number of publications on surgical treatment of NSCLC in the elderly is increasing, but results are difficult to compare. Main problem is the absence of a clear definition of the elderly patient. Geriatric oncology has been operationally defined as “when the health status of a patient population begins to interfere with the oncological decision making guidelines”9 and recommends that decision making is to be governed by the patient’s performance status rather than by a fixed age limit.10 However, age limits of 65, 70, 75, or 80 years can still be found in the literature.11–14 The median life expectancy of octogenarians in general, 6 years for men and 8 for women, is relatively long compared with the1.5 years for patients with untreated or palliated resectable NSCLC. It is clear that the life-limiting factor in these octogenarians is not their age but rather their

Copyright © 2007 by the International Association for the Study of Lung Cancer

1015

Brokx et al.

Journal of Thoracic Oncology • Volume 2, Number 11, November 2007

cancer.15 Surgery therefore offers better prospects with respect to length and quality of life than conservative management.16 Our data from the Amsterdam Cancer Registry show the better relative survival of clinical stage I/II octogenarians treated surgically compared with radiotherapy or no or other treatment modalities (52% versus 6% and 2%, respectively). Conventional radiotherapy can be an alternative for patients with medical contraindications; however, it is associated with the risk of severe side effects and permanent decrease in lung function, which is reflected in these survival figures. Unfortunately, as comorbidity has not been scored, it remains unclear to what extent preexisting comorbidity or treatment toxicity of radiotherapy contributed to the worse outcome in these patients. Fourteen percent of the NSCLC diagnoses in our study were made in octogenarians. The actual figure may be slightly higher due to underascertainment and underregistration. Elderly patients are less likely to be referred to hospital, and tumors are less often verified by microscopic examination. Moreover, older patients tend to be less accurately staged and are often not treated according to protocol.17 With the gradually increasing life expectancy in the Western world, the number of elderly patients demanding adequate treatment may increase considerably in the near future. The low proportion of surgically treated octogenarians (6%) may be explained by the high prevalence of comorbidity at this age; unfortunately, comorbidity data were not available for analysis. In a recent population-based study from a different area of The Netherlands, the health status of the patients was also recorded. Nine percent of the octogenarians underwent surgery, but also in this study, the percentage was lower than expected according to the comorbidity profile.5 Our study shows that the outcome of surgically treated octogenarians with NSCLC is satisfying, even in a large region where patients are mainly treated in general hospitals, especially if we look at the comparable relative survival of surgically treated octogenarians relative to the other age groups in the split sample analysis. Whether the results could be improved is unknown. Given recent publications on better outcome in high-volume hospitals,18 discussions on concentration of lung surgery need to be started. Eighty-five percent of the patients underwent a real oncologic resection, removal of the primary tumor with the area of lymph drainage. Only 5% had a sublobar resection. Lobectomy is still considered the minimal oncologic resection in NSCLC,19 although recent papers state that smaller resections should be considered in elderly patients because the outcome is not severely affected.17,20 In our study, the proportion of pneumonectomies was high compared with other studies16,21–23 and comprised 12 resections of the left lung and three of the right. Right-sided resection carries a high complication rate and needs to be avoided in elderly patients.24 A wider application of sleeve-resections might have reduced the number of pneumonectomies. Information on postoperative complications was also not recorded. The postoperative mortality of 4% and the relative 5-year survival rate of 47% are comparable with results reported for octogenarians in the literature4,11,12,16,21–23,25,26 and are

1016

noteworthy considering the participation of many nonspecialized centers. These relative survival rates for octogenarians equal those for the other age groups in the studied region. There are some limitations to our study. First, presurgical selection and patients comorbidities have not been scored. Second, because of its retrospective nature and anonymous registration, quality-of-life analysis could not be performed. Despite these limitations, the current study has an important strength in that it provides insight into the number of surgical resections for lung cancer in octogenarians being performed with their accompanying absolute and relative survival. These numbers clearly show that, although the selection criteria for surgical resection are not exactly known, the relative 5-year survival of octogenarians after resection is comparable with the other age groups. Furthermore, relative survival rates for surgically treated stage I/II octogenarians are better than for clinical stage I/II octogenarians receiving radiotherapy or no therapy. This study was a population-based study and thus provides far better insight than most of the previously published studies, which were mostly conducted based on specialized single-center figures. Thoracic surgery, therefore, seems to be safe and feasible in this group of selected elderly patients. The criteria used for selection, although not exactly known, seem to function well, as long as a comprehensive preoperative assessment is performed to select surgical candidates appropriately. However, several questions remain. First, how many elderly patients could have received potential curative resection if less strict criteria were applied and a higher mortality rate would have been accepted? There is no consensus on the mortality risk at which surgery is no longer acceptable. According to Cykert,27 in the absence of other treatment possibilities, patients tend to accept very high operative risks. Furthermore, it is said that older patients tend to reject treatment options if the outcome implies chronic morbidity and long-term dependency.28 Second, a higher resection rate might be obtained without increasing the mortality, just by concentration of care in high-volume hospitals with a comprehensive approach for treating elderly people. Third, one should not focus on mortality rates alone because quality-of-life issues should influence decision making as well. For example, in the study of Osaki et al.,12 the 30-day mortality rate was 3%, but 18% of the remaining patients never left the hospital. Because of this quality-of-life issue, new treatment options may play an important role in the future. When elderly patients are offered less aggressive treatment strategies, they are more inclined to choose these alternatives.27 Stereotactic limited-field radiotherapy is reported to offer results comparable with those of resection in localized NSCLC, without the known adverse effects of conventional radiotherapy.29,30 With modern staging tools such as positron emission tomography (PET) and ultrasonography-guided endoscopy, accurate staging can be performed and this stereotactic radiotherapy option should be considered in frail patients.

Copyright © 2007 by the International Association for the Study of Lung Cancer

Journal of Thoracic Oncology • Volume 2, Number 11, November 2007 Surgical Treatment for Octogenarians with Lung Cancer

CONCLUSION Fourteen percent of NSCLC occurs in patients 80 years and older. Only 6% of them underwent resection, with acceptable postoperative mortality, even in low-volume hospitals. Relative survival for surgically treated octogenarians was comparable with that of other younger age groups, and there was a relative survival benefit for octogenarians with clinical stage I/II lung cancer treated surgically relative to octogenarians undergoing radiotherapy or no/other therapy. Until effective alternatives become available, surgical resection (preceded by meticulous preoperative assessment) should be and can be offered to the “old but fit” octogenarian. REFERENCES 1. Yancik R, Ries AL. Aging and cancer in America. Demographic and epidemiologic perspectives. Hematol Oncol Clin North Am 2000;14:17– 23. 2. Breyer RH, Zippe C, Pharr WF, et al. Thoracotomy in patients over age seventy years; ten-year experience. J Thorac Cardiovasc Surg 1981;81: 187–193. 3. Ginsberg RJ, Hill L, Eagan RT, et al. Modern thirty-day operative mortality for surgical resections in lung cancer. J Thorac Cardiovasc Surg 1983;86:654–658. 4. Shirakusa T, Tsutsui M, Iriki N, et al. Results of resection for bronchogenic carcinoma in patients over the age of 80. Thorax 1989;44:189– 191. 5. Janssen-Heijnen ML, Smulders S, Lemmens VE, et al. Effect of comorbidity on the treatment and prognosis of elderly patients with non-small cell lung cancer. Thorax 2004;59:602–607. 6. Lewis JH, Kilgore ML, Goldman DP, et al. Participation of patients 65 years of age or older in cancer clinical trials. J Clin Oncol 2003;21: 1383–1389. 7. Hutchins LF, Unger JM, Crowley JJ, et al. Underrepresentation of patients 65 years of age or older in cancer-treatment trials. N Engl J Med 1999;341:2061–2067. 8. Damhuis R, Coonar A, Plaisier P, et al. A case-mix model for monitoring of postoperative mortality after surgery for lung cancer. Lung Cancer 2006;51:123–129. 9. Extermann M. Measuring comorbidity in older cancer patients. Eur J Cancer 2000;36:453–471. 10. Roxburgh JC, Thompson J, Goldstraw P. Hospital mortality and longterm survival after pulmonary resection in the elderly. Ann Thorac Surg 1991;51:800–803. 11. Naunheim KS, Kesler KA, D’Orazio SA, et al. Lung cancer surgery in the octogenarian. Eur J Cardiothorac Surg 1994;8:453–456. 12. Osaki T, Shirakusa T, Kodate M, et al. Surgical treatment of lung cancer in the octogenarian. Ann Thorac Surg 1994;57:188–193.

13. Damhuis RA, Schutte PR. Resection rates and postoperative mortality in 7,899 patients with lung cancer. Eur Respir J 1996;9:7–10. 14. Massard G, Moog R, Wihlm JM, et al. Bronchogenic cancer in the elderly: operative risk and long-term prognosis. Thorac Cardiovasc Surg 1996;44:40–45. 15. Yellin A, Benfield JR. Surgery for bronchogenic carcinoma in the elderly. Am Rev Respir Dis 1985;131:197. 16. Brock MV, Kim MP, Hooker CM, et al. Pulmonary resection in octogenarians with stage I non-small cell lung cancer: a 22-year experience. Ann Thorac Surg 2004;77:271–277. 17. Jaklitsch MT, Mery CM, Audisio RA. The use of surgery to treat lung cancer in elderly patients. Lancet Oncol 2003;4:463–471. 18. Bach PB, Cramer LD, Schrag D, et al. The influence of hospital volume on survival after resection for lung cancer. N Engl J Med 200119;345: 181–188. 19. Ginsberg RJ, Rubinstein LV. Randomized trial of lobectomy versus limited resection for T1N0 non-small cell lung cancer. Ann Thorac Surg 1995;60:615–623. 20. Mery CM, Pappas AN, Bueno R, et al. Similar long-term survival of elderly patients with non-small cell lung cancer treated with lobectomy or wedge resection within the surveillance, epidemiology and end results database. Chest 2005;128:237–245. 21. Pagni S, Federico JA, Ponn RB. Pulmonary resection for lung cancer in octogenarians. Ann Thorac Surg 1997;63:785–789. 22. Wada H, Nakamura T, Nakamoto K, et al. Thirty-day operative mortality for thoracotomy in lung cancer. J Thorac Cardiovasc Surg 1998; 115:70–73. 23. Hanagiri T, Muranaka H, Hashimotot M, et al. Results of surgical treatment of lung cancer in octogenarians. Lung Cancer 1999;23:129– 133. 24. van Meerbeek JP, Damhuis RAM, Vos de Wael ML. High postoperative risk after pneumonectomy in elderly patients with right-sided lung cancer. Eur Respir J 2002;19:141–145. 25. Aoki T, Yamato Y, Tsuchida M, et al. Pulmonary complications after surgical treatment of lung cancer in octogenarians. Eur J Cardiothorac Surg 2000;18:662–665. 26. Port JL, Kent M, Korst LJ, et al. Surgical resection for lung cancer in the octogenarian. Chest 2004;126:733–738. 27. Cykert S. Risk acceptance and risk aversion: patients’ perspectives on lung surgery. Thorac Surg Clin 2004;14:287–293. 28. Weinman M, Jeremic B, Toomes H, et al. Treatment of lung cancer in the elderly. Part I: Non-small cell lung cancer. Lung Cancer 2003;39: 233–253. 29. Fukumoto S, Shirato H, Shimzu S, et al. Small-volume image-guided radiotherapy using hypofractionated, coplanar, and noncoplanar multiple fields for patients with inoperable nonsmall cell lung carcinomas. Cancer 2002;95:1546–1553. 30. Onishi H, Araki T, Shirato H, et al. Stereotactic hypofractionated high-dose irradiation for stage I nonsmall cell lung carcinoma: clinical outcomes in 245 subjects in a Japanese multiinstitutional study. Cancer 2004;101:1623–1631.

Copyright © 2007 by the International Association for the Study of Lung Cancer

1017